Although impulsivity is a complex construct which has genetic, environmental, and neurophysiologic etiologies, it is likely that at least part of the increased impulsivity seen in cocaine dependent subjects is due the effects of chronic cocaine use on prefrontal cortical brain function. It is also likely that the negative treatment outcome in impulsive cocaine users is largely due to cognitive deficits related to changes in the prefrontal cortex that interfere with treatment for cocaine dependence. The overall aim of this component of the P50 is to determine how impulsivity and prefrontal cortical function are related to treatment response in cocaine dependent subjects. Impulsivity will be measured by a battery of self-report and behavioral laboratory tasks. Attention, working memory, and executive cognitive function will be measured by a battery of neuropsychological tests. Prefrontal cortical function will be measured by functional magnetic resonance imaging, and frontal cortical white matter integrity will be measured by diffusion tensor imaging. It is hypothesized that impulsivity will be related to impairment in cognitive function and prefrontal cortical structure and function in cocaine dependent subjects. It is further hypothesized that alterations in cognitive and prefrontal cortical function and structure will predict a poorer treatment response in cocaine dependent subjects, and that treatment with modafinil will improve these measures in cocaine dependent subjects. This project integrates the analytical strengths of physicists and behavioral scientists to focus on the problem of basic brain mechanisms underlying cocaine dependence, as described in the NIH Roadmap. Cocaine dependence continues to be a significant health problem within the United States. Likewise, impulsivity is associated with a number of public health related issues, including violence and risky sexual behavior which increases the risk for HIV/AIDS. A greater understanding of the basic mechanisms of impulsivity in cocaine dependence could lead to development of treatments for impulsivity and cocaine dependence.